Chylomicrons triglycerides, hydrolysis

The substrate for the LPL is the triglyceride contained within the oily core of VLDL particles and chylomicrons. The fatty acids and monoglycerides liberated from triglyceride hydrolysis are taken into the adipocytes and reformed into neutral fat for calorie storage (Figure 9.11). The ultimate result of the delipidation of VLDL and chylomicrons to the formation of low-density lipoproteins (LDL) as described in Section 5.5. 

There is good evidence that nascent chylomicrons acquire apoC and apoE from HDL present in lymph and blood plasma (G28, 14). The fete of apoE during the hydrolysis of chylomicron triglyceride by lipoprotein lipase is unknown. Perhaps some apoE is lost to the HDL fraction during lipolysis, in the same way that redundant phospholipid and apoC are lost (H17, M38). 

Lipoprotein lipase, an extracellular enzyme, causes the hydrolysis of VLDL and chylomicron triglycerides. Hormone-sensitive lipase catalyzes the hydrolysis of intracellular (storage) triglyceride. 

During the initial hydrolysis of chylomicron triglycerides by LPL, apoA-I and phospholipids are shed from the surface of chylomicrons and remain in the plasma. This is one mechanism by which nascent (precursor) HDL are generated. Chylomicron remnants are not precursors of LDL, but the dietary cholesterol delivered to the liver by remnants increases plasma LDL levels by reducing LDL receptor-mediated catabolism of LDL by the liver. 

Chylomicrons and remnants 1.006 Dietary triglycerides and cholesterol 10 1 B-48, E, A-L A-IV, C-L C-II, C-III Intestine Triglyceride hydrolysis by LPL ApoE-mediated remnant uptake by liver... 

Plasma VLDL is catabolized by LPL in the capillary beds in a process similar to the lipolytic processing of chylomicrons (Figure 35—1). When triglyceride hydrolysis is nearly complete, the VLDL remnants, usually termed intermediate-density lipoproteins (IDL), are released from the capillary endothelium and reenter the circulation. ApoB-100 containing small VLDL and IDL, which have a tj 2 minutes, have two potential fates 40-60% are cleared from the plasma... 

Chylomicrons Triglycerides 80-95%, free cholesterol 1-3%, cholesterol esters 2-4%, phospholipids 3-9%, apoproteins 1-2% apoA-l, apoA-IV, apoB-48, apoC-l, apoC-ll, apoC-lll Transport dietary triglycerides to adipose tissue and muscle for hydrolysis by lipoprotein lipase. 

They can be synthesized by the gut, following the absorption of hydrolyzed dietary lipid. They are combined with small amounts of protein, cholesterol and phospholipid to form chylomicrons. These are removed from the blood, mainly by adipose tissue. An enzyme, lipoprotein lipase is responsible for this hydrolysis of the chylomicron triglycerides. The free fatty acids liberated by these processes are resynthesized into triglycerides by the adipose tissue and stored. 

Endothelial anchored enzyme in muscle and adipose tissue primarily responsible for hydrolysis of chylomicron and VLDL triglycerides. 

Triglycerides are removed in extrahepatic tissues through a pathway shared with VLDL that involves hydrolysis by the lipoprotein lipase (LPL) system. Decrease in particle diameter occurs as triglycerides are depleted. Surface lipids and small apoproteins are transferred to HDL. The resultant chylomicron remnants are taken up by receptor-mediated endocytosis into hepatocytes. 

LCAT), which catalyzes the synthesis of cholesterol esters (F14, S46, S59) apoA-II, which activates hepatic triglyceride lipase (J2) and apoC-II, which activates lipoprotein lipase, responsible for the hydrolysis of triglycerides in chylomicrons and VLDL (H20, L5). Their mode of action is considered in Section 4 when the individual apolipoproteins are discussed. 

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

Lipoprotein lipase (EC 3.1.1.34) is an enzyme or group of enzymes which catalyze the hydrolysis of the 1(3) ester bond(s) of triacylglycerols and the 1 ester bond of phospholipids. The enzyme plays a central role in lipoprotein metabolism, being responsible in particular for the hydrolysis of chylomicron and VLDL triglycerides and the formation of remnant particles from these lipoproteins. There have been reviews of this enzyme [e.g., (N9, Ql)] and lipoprotein lipase will not be discussed in detail in this review. Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism have also been reviewed (B58, N8) and will not be discussed in detail. 

Chylomicrons are triglyceride rich and contain apolipoprotein B-48 and the A types. The latter are synthesized in the intestinal tract cells. Additional apoproteins are transferred to the chylomicrons from HDL in circulation the apoE and apoC types. Their site of synthesis is the liver. The chylomicrons are subject to degradation by lipoprotein lipase in the peripheral tissue, especially adipose tissue. Lipoprotein lipase activity is increased by increased blood insulin levels. This enzyme is extracellular, attached to the capillary endothelial cells, and activated by ApoC-II, which is present in the chylomicrons. Lipoprotein lipase causes the hydrolysis of triglycerides, thus decreasing chylomicron size... 

This disorder is characterized by marked hyperchylomi-cronemia and a corresponding hypertriglyceridemia (triglyceride as high as 10,000 mg/dL). As discussed previously, LPL is essential for the hydrolysis of triglyceride and the conversion of chylomicrons to chylomicron remnants. The massive accumulation of chylomicrons in the circulation indicates the inability to catabolize dietary fat. The concentration of VXDL cholesterol is usually normal and the concentrations of HDL cholesterol and LDL cholesterol are low (type I pattern). Furthermore, the concentration of apo C-II, the activator of LPL, is normal. 

LPL is the major enzyme involved in the processing of chylomicrons and VLDL by hydrolysis of fatty acids from triglycerides. Phospholipids may also serve as substrates for LPL. Apo C-III inhibits the activation of LPL by apo C-II in vitro, albeit at high levels, but the physiological importance of inhibition is not understood. 

Role of lipoprotein lipase Hydrolysis of triglycerides from VLDL and chylomicrons... 

Lipoprotein lipase (LPL) An enzyme bonnd to the surface of the capillary endothehum by heparan sulfate proteoglycans. LPL catalyzes the hydrolysis of triglyceride in chylomicrons and VLDL to free fatty acids and glycerol. 

Dietary lipids (triglycerides) are emulsified into tiny fat droplets in the intestine by the action of bile salts. Pancreatic lipase catalyzes the hydrolysis of triglycerides into monoglycerides and fatty acids. These are absorbed by intestinal epithelial cells, reassembled into triglycerides, and combined with protein to form chylomicrons. Chylomicrons are transported to the cells of the body through the bloodstream. Fatty acids are stored as triglycerides (triacylglyc-erols) in fat droplets in the cytoplasm of adipocytes. 

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